Validation of the AJCC 8th Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01)

Abstract

Background: The 8th edition American Joint Committee on Cancer staging system combined anatomic stage (AS) with receptor status and grade to create prognostic stage (PS). PS has been validated in single-institution and cancer registry studies; however, missing human epidermal growth factor receptor 2 (HER2) status and variable treatment and follow-up create limitations.

Objective: Our objective was to compare the relative prognostic ability of PS versus AS to predict survival using breast cancer clinical trial data.

Methods: Women with non-metastatic breast cancer enrolled in six Alliance for Clinical Trials in Oncology trials were included (enrollment years 1997-2010). AS and PS were constructed using pathological tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR), HER2 status, and grade. Unadjusted Cox proportional hazard models were estimated to predict overall survival within 5 years, with AS and PS as predictor variables. The relative predictive power of staging models was assessed by comparing Harrell concordance indices (C-indices). Kaplan-Meier-based mortality estimates were compared by stage.

Results: Overall, 6924 women were included (median age 53 years); 45.2% were diagnosed with ER+/PR+/HER2- tumors, 26.2% with HER2+ tumors, and 17.1% with ER-/PR-/HER2- tumors. Median follow-up time was 5 years (interquartile range 2.95-5.00). PS significantly improved predictive performance (C-index 0.721) for overall survival compared with AS (0.700) (p = 0.020). Kaplan-Meier hazard estimates suggested PS did not distinguish mortality risk between patients with IIB and IIIA or IB and IIA disease.

Conclusions: PS has significantly improved predictive performance for OS compared with AS. As systemic therapies evolve, it will be important to re-evaluate the prognostic staging system, particularly for patients with intermediate-stage cancers.

Clinicaltrials: gov Identifier: NCT02171078.

Keywords: American Joint Committee on Cancer; Anatomic stage; Breast cancer; Clinical trial; Prognostic stage.